Abstract
Understanding the principles of protein packing and the mechanisms driving morphological transformations in virus shells (capsids) during their maturation can be pivotal for the development of new antiviral strategies. Here, we study how these principles and mechanisms manifest themselves in icosahedral viral capsids assembled from identical symmetric structural units (capsomeres). To rationalize such shells, we model capsomers as symmetrical groups of identical particles interacting with a short-range potential typical of the classic Tammes problem. The capsomere particles are assumed to retain their relative positions on the vertices of planar polygons placed on the spherical shell and to interact only with the particles from other capsomeres. Minimization of the interaction energy enforces equal distances between the nearest particles belonging to neighboring capsomeres and minimizes the number of different local environments. Thus, our model implements the Caspar and Klug quasi-equivalence principle and leads to packings strikingly similar to real capsids. We then study a reconstruction of protein trimers into dimers in a Flavivirus shell during its maturation, connecting the relevant structural changes with the modifications of the electrostatic charges of proteins, wrought by the oxidative switch in the bathing solution that is essential for the process. We highlight the key role of pr peptides in the shell reconstruction and show that the highly ordered arrangement of these subunits in the dimeric state is energetically favored at a low pH level. We also discuss the electrostatic mechanisms controlling the release of pr peptides in the last irreversible step of the maturation process.